Umbilical Cord & Wharton’s Jelly

This study aimed to explore alternative sources of mesenchymal stromal cells (MSC), as deriving cells from bone marrow is an invasive procedure. The study sought out more accessible sources of MSC, such as from amnion, placenta, Wharton’s jelly and umbilical cord, which are usually discarded. The study concluded that these alternative sources may potentially be used in place of bone marrow-derived MSCs in several therapeutic applications.

This study focused on the immune characterizations of mesenchymal stem cells, derived from Wharton’s jelly found in human umbilical cords. It was found that these cells have very low immunogenicity and good potential to tolerate rejection. Their intermediate state between adult and embryonic stem cells makes them an ideal candidate for reprogramming to the pluripotent status.

Compared with human bone marrow-derived mesenchymal stem cells (hBMSCs), human umbilical cord-derived mesenchymal stromal cells (hUCMSCs) have the advantages of abundant supply, painless collection, no donor site morbidity, and faster and longer self-renewal in vitro. In this 6-week study, a chondrogenic (forming cartilage from condensed mesenchyme tissue) comparison was conducted of hBMSCs and hUCMSCs in a three-dimensional (3D) scaffold for the first time.

The results of this study suggest that it is safe and feasible to provide cell therapy with intravenous infusion of bone marrow‐derived mesenchymal stem cells (MSCs) to lung transplant recipients with moderate obstructive CLAD, warranting future studies to assess the effectiveness of this therapy for management of acute or chronic graft dysfunction.

Comparative Characterization of Cells from the Various Compartments of the Human Umbilical Cord Shows that the Wharton’s Jelly Compartment Provides the Best Source of Clinically Utilizable Mesenchymal Stem Cells

The human umbilical cord (UC) is an attractive source of mesenchymal stem cells (MSCs) with unique advantages over other MSC sources. They have been isolated from different compartments of the UC but there has been no rigorous comparison to identify the compartment with the best clinical utility. This study compared the histology, fresh and cultured cell numbers, morphology, proliferation, viability, stemness characteristics and differentiation potential of cells from the amnion (AM), subamnion (SA), perivascular (PV), Wharton’s jelly (WJ) and mixed cord (MC) of five UCs.

Taken together, it appears that MSCs from the Wharton’s jelly are more superior than those from the PV, SA, AM and MC in terms of clinical utility and research value because: (i) their isolation is simple, quick and easy to standardize, (ii) they have lesser non-stem cell contaminants (iii) they are rich in stemness characteristics, (iv) they can be generated in large numbers with minimal manipulation, (v) they are proliferative and (vi) have broad and efficient differentiation potential. They will thus be stable and attractive candidates for research and future cell-based therapies when derived, propagated and characterized correctly.

The results of this study show that when isolating MSCs from the umbilical cord, the Wharton’s jelly should be the preferred compartment, and a standardized method of derivation must be used so as to make meaningful comparisons of data between research groups.

Different populations and sources of human mesenchymal stem cells (MSC): A comparison of adult and neonatal tissue-derived MSC

Mesenchymal stem cells (MSC) from birth-associated tissues, preferably parts of the placenta and the umbilical cord/Wharton’s jelly (UC- and WJ-MSC) may offer certain advantages. These include their non-invasive and ethically non-problematic availability. More importantly, MSC from these neonatal tissues possess increased proliferative (to multiply rapidly producing more tissue) capacity in vitro, in comparison to some MSC populations obtained from adult tissues.

The umbilical cord matrix is a better source of mesenchymal stem cells (MSC) than the umbilical cord blood

According to the critical parameters of sample selection described in this study, and using different culture media proposed to enhance the growth of mesenchymal stem cells (MSC), in parallel with the use of different methods of cell isolation, the researchers were not able to establish MSC cultures from more than one out of 15 UCB samples. Given the high frequency of MSC in UCM, the study hypothesizes that there may be MSC contamination while collecting cord blood. This may explain the rare described cases where MSC isolation from UCB has been possible. However, it could not be ascertained whether the collection method may have caused the disappearance of circulating MSC from the cord blood MNC compartment in favor of the endothelial/subendothelial layer of the UCM. They conclude that UCB can be excluded as a reliable source of MSC in favor of the richer and more reproducible source that is the UCM, meaning the umbilical cord matrix (UCM) is a better source of mesenchymal stem cells (MSC) than the umbilical cord blood (UCB).

Umbilical Cord Tissue Offers the Greatest Number of Harvestable Mesenchymal Stem Cells for Research and Clinical Application: A Literature Review of Different Harvest Sites

This study discusses how large variations in cell harvest yields remain for each major tissue site for mesenchymal stem cells (MSCs) as reported in literature to date. Reviewed research supports the understanding that placental tissue provides the highest concentration of cells whereas adipose tissue offers the highest levels of autologous cells. Consequently, considerations must be made regarding the non-autologous nature of umbilical cord derived stem cells, as well as the increased post-harvest processing required for adipose-derived stem cells, for the purposes of research and clinical application.

This study discusses how Wharton’s jelly is a predominantly good source of cells because mesenchymal stem cells (MSCs) in Wharton’s jelly (WJ-MSC) are maintained in a very early embryological phase and therefore have retained some of the primitive stemness properties. WJ-MSCs can easily differentiate into a plethora of cell types leading to a variety of applications. WJ-MCSs are still the ideal future for cell therapy; their properties of high proliferation capability and versatility to differentiate between three lineages allow them to lower immunogenicity and have the potential to treat an array of diseases and disorders.

In this study, there was no obvious chromosome elimination, displacement, or chromosomal imbalance as determined from the guidelines of the International System for Human Cytogenetic Nomenclature. Telomerase activity was down-regulated significantly when the culture time was prolonged. Further, no tumors formed in rats injected with human umbilical cord mesenchymal stem cells (hUC-MSCs) cultured in serum-free and in serum containing conditions.

This study concluded that their data showed that hUC-MSCs met the International Society for Cellular Therapy sandards for conditions of long-term in vitro culturing. Since hUC-MSCs can be safely expanded in vitro and are not susceptible to malignant transformation in serum-free medium, these cells are suitable for cell therapy.

Taken together, Wharton’s jelly mesenchymal stem cells (WJ-MSCs) display decreased cellular senescence after extended in vitro culture, increased proliferative capacity and reduced potential to differentiate in vitro to adipocytes and osteocytes, as compared to bone marrow mesenchymal stem cells (BM-MSCs). The last two observations can be explained, at least partly, by the aberrant expression of Wnt-signaling molecules in WJ-MSCs. The emerging role of Wnt-signaling pathway in WJ-MSC biology is currently under investigation.

This study suggests there is accumulating interest in identifying alternative sources for mesenchymal stem cells (MSCs). To this end MSCs obtained from the Wharton’s Jelly (WJ) of umbilical cords (UC) have gained much attention over the years since they can be easily isolated, without any ethical concerns, from a tissue which is discarded after birth. Furthermore, MSCs derived from Wharton’s Jelly represent a more primitive population than their adult counterparts, opening new perspectives for cell-based therapies.

In this review, they first give an overview of the biology of MSCs derived from the umbilical cord Wharton’s Jelly. They then look at these MSCs potential application for the treatment of cancer and immune mediated disorders, such as graft versus host disease (GVHD) and systemic lupus erythematosus (SLE). Finally, their putative role as feeder layer for ex vivo hematopoietic stem cell (HSC) expansion is pointed out.

Taken together, the clinical implication of oxidative stress, telomere length, DNA damage and disease has impaired the therapeutic potential of mesenchymal stem cells (MSC) isolated from aged patients. These changes in MSC biology indicate that aged patients may require an alternative source of stem cells for treatment. The high efficiency of Wharton’s Jelly mesenchymal stem cells (WJ-MSC) recovery, the minimal ethical concerns associated with its acquirement and use, low immunogenicity, and the fact that they are from healthy, young donors make them an ideal source of MSC for autologous and allogeneic applications.

Wharton’s jelly as a reservoir of peptide growth factors

The amounts of peptide growth factors calculated per microgram of DNA are distinctly higher in Wharton’s jelly in comparison to the umbilical cord artery. Western blot analysis demonstrated that almost the entire amount of these factors is bound to high molecular weight components. Since the number of cells in Wharton’s jelly is very low and the amounts of extracellular matrix components are very high, it is concluded that the cells are strongly stimulated by peptide growth factors to produce large amounts of collagen and glycosaminoglycans.

Mesenchymal stem cells (MSCs), isolated from human umbilical cord Wharton’s Jelly, were capable of differentiating into nerve-like cells using Salvia miltiorrhiza or beta-mercaptoethanol. The induced MSCs not only underwent morphologic changes, but also expressed the neuron-related genes and neuronal cell markers. They may represent an alternative source of stem cells for central nervous system cell transplantation.

Perspectives of employing mesenchymal stem cells from the Wharton’s jelly of the umbilical cord for peripheral nerve repair

Mesenchymal stem cells (MSCs) from Wharton’s jelly present high plasticity and low immunogenicity, making them a desirable form of cell therapy for an injured nervous system. Their isolation, expansion, and characterization have been performed from cryopreserved umbilical cord tissue. The MSCs from Wharton’s jelly delivered through tested biomaterials should be regarded a potentially valuable tool to improve clinical outcome especially after trauma to sensory nerves. In addition, these cells represent a noncontroversial source of primitive mesenchymal progenitor cells, which can be harvested after a healthy birth, cryogenically stored, thawed, and expanded for therapeutic uses.

Stem Cell Technology for Neurodegenerative Diseases

Over the past 20 years, stem cell technologies have become an increasingly attractive option to investigate and treat neurodegenerative diseases. This study explains the various types of stem cells utilized in neurodegenerative disease research and details the current progress regarding the applications of stem cell therapies to specific neurodegenerative diseases, focusing on Parkinson’s disease, Huntington’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis and spinal muscular atrophy. As this study mentions, there is growing public hope that stem cell therapies will continue to progress into realistic and efficacious treatments for neurodegenerative diseases.

Mesenchymal stem cells to treat diabetic neuropathy: a long and strenuous way from bench to the clinic

This study discusses how diabetic neuropathy (DN) frequently leads to foot ulcers and ultimately limb amputations without effective clinical therapy. DN is characterized by reduced vascularity in the peripheral nerves and deﬁciency in angiogenic and neurotrophic factors. Only delivering neurotrophic or angiogenic factors for treatment in the form of protein or gene therapy is very modest if not ineffective.

Mesenchymal stem cells (MSCs) have been highlighted as a new emerging regenerative therapy owing to their multipotency for DN. MSCs reverse manifestations of DN, repair tissue, and antihyperglycemia. MSCs also paracrinely secrete neurotrophic factors, angiogenic factors, cytokines, and immunomodulatory substances to ameliorate DN.

Mesenchymal Stem Cells as a Prospective Therapy for the Diabetic Foot

The diabetic foot is a serious complication of diabetes. Mesenchymal stem cells (MSCs) are an abundant source of stem cells which occupy a special position in cell therapies, and recent studies have suggested that mesenchymal stem cells can play essential roles in treatments for the diabetic foot. This study discusses the advances that have been made in mesenchymal stem cell treatments for this condition. The roles and functional mechanisms of mesenchymal stem cells in the diabetic foot are also summarized, and insights into current and future studies are presented.

Perspectives of employing mesenchymal stem cells from the Wharton’s jelly of the umbilical cord for peripheral nerve repair

Mesenchymal stem cells (MSCs) from Wharton’s jelly present high plasticity and low immunogenicity, turning them into a desirable form of cell therapy for the injured nervous system. Their isolation, expansion, and characterization have been performed from cryopreserved umbilical cord tissue. Great concern has been dedicated to the collection, preservation, and transport protocols of the umbilical cord after the parturition to the laboratory in order to obtain samples with higher number of viable MSCs without microbiological contamination.

Orthopedic Conditions & Sports Injuries

Characteristics of mesenchymal stem cells derived from Wharton’s jelly of human umbilical cord and for fabrication of non-scaffold tissue-engineered cartilage

Once cartilage is damaged, it has limited potential for self-repair. Autologous chondrocyte implantation is an effective treatment, but patients may suffer during cartilage harvesting and the donor-site morbidity may accelerate joint degeneration. Using autologous mesenchymal stem cells (MSCs) derived chondrocytes is another selection, while it also causes some injuring. The umbilical cord, an ecto-embryo tissue may be an ideal source of cells, because of its accessibility, abundant resources, painless procedures for harvesting, and lack of ethical issues. MSCs isolated from Wharton’s jelly of human umbilical cord express characteristics of pre-chondrocytes, low immunogenicity and are easy to be obtained with higher purity because there have no hematopoietic cells in Wharton’s jelly, so it may be a new seed cells more suitable for constructing tissue-engineered cartilage.

This study focuses on stem cell based therapeutics for . cartilage and intervertebral disc (IVD) repair. It concludes that mesenchymal stem cell based therapies offer huge potential to revolutionize the treatment of cartilage defects and IVD degeneration

Rotator cuff tendon tear is one of the most common causes of chronic shoulder pain and disability. In this study, they investigated the therapeutic effects of ultrasound‐guided human umbilical cord blood (UCB)‐derived mesenchymal stem cell (MSC) injection to regenerate a full‐thickness subscapularis tendon tear in a rabbit model by evaluating the gross morphology and histology of the injected tendon and motion analysis of the rabbit’s activity.

This study concluded that UCB‐derived MSC injection under ultrasound guidance without surgical repair or bioscaffold resulted in the partial healing of full‐thickness rotator cuff tendon tears in a rabbit model. Histology revealed that UCB‐derived MSCs induced regeneration of rotator cuff tendon tears and that the regenerated tissue was predominantly composed of type I collagens. In addition, motion analysis showed better walking capacity after MSC injection than HA or normal saline injection. These results suggest that ultrasound‐guided UCB‐derived MSC injection may be a useful conservative treatment for full‐thickness rotator cuff tendon tear repair.

The study concluded that the IGF1-induced WJMSCs were capable to enhance chondrogenesis, indicated by increased expression of SOX9 and COL2 and decreased expression of ADAMTS1, ADAMTS5, MMP3, MMP1, and RANKL. These findings can be further used in the osteoarthritis treatment.

Effect of nicotine on the proliferation and chondrogenic differentiation of the human Wharton’s jelly mesenchymal stem cells

Osteoarthritis (OA) is a chronic joint disease characterized by a progressive and irreversible degeneration of articular cartilage. Among the environmental risk factors of OA, tobacco consumption features prominently, although, there is a great controversy regarding the role of tobacco smoking in OA development. Among the numerous chemicals present in cigarette smoke, nicotine is one of the most physiologically active molecules.

At the concentration used, the study concluded that nicotine had an adverse effect on the proliferation and chondrogenic differentiation of mesenchymal stem cells from the human Wharton’s jelly (hWJ-MSCs).

This study suggests that after the acquisition of a mature phenotype, Wharton’s jelly mesenchymal stem cell (WJMSCs)-derived cells may maintain their immune privilege. This evidence, which deserves much work to be confirmed in vivo and in other mesenchymal stem cells (MSCs) populations, may provide a formal proof of the good results globally achieved with WJMSCs as cellular therapy vehicle.

Cell-based cartilage repair procedures are becoming more widely available and have shown promising potential to treat a wide range of cartilage lesion types and sizes, particularly in the knee joint. This study presents a technique of cartilage repair in the knee using Wharton’s jelly–derived mesenchymal stem cells (MSCs) embedded onto scaffolding and implanted in a minimally invasive fashion using dry arthroscopy.

The ability of these cells to promote chondrogenesis, without eliciting an immunogenic response, makes them an excellent candidate for providing cell-based cartilage repair in an off-the-shelf fashion. Moreover, use of Wharton’s jelly mesenchymal stem cells (WJ-MSCs) for cartilage repair in older patients will address concerns related to MSC number and immunomodulatory capacity with autologous harvest in aging patients, making this technique a promising advancement in the treatment of cartilage injury for this demographic.

Role of mesenchymal stem cells in osteoarthritis treatment

Without an effective cure, Osteoarthritis (OA) remains a significant clinical burden on our elderly population. The advancement of regenerative medicine and innovative stem cell technology offers a unique opportunity to treat this disease. In this study, they examine OA and the likely resolution with mesenchymal stem cells (MSCs). MSCs have been one of the highlights in stem cell research in recent years. Although the application of MSCs in joint repair is well established, it is particularly exciting about MSCs being used for OA treatment.

Mesenchymal stem cells for cartilage regeneration in osteoarthritis

In summary, this study shows that mesenchymal stem cells (MSCs) can be employed successfully to treat mild to moderate osteoarthritis (OA) through various ways. They provide alternative treatment options and treatment can start early during progression of OA. The traditional major surgeries used to treat late stages are expensive and come with risks. The less invasive techniques outlined in this review have revealed good outcomes, but the field merits further investigation. Superior outcome was evident with greater quantity of MSCs injected. Allogenic cells from healthy young donors can also be utilized. These findings have further empowered researchers to investigate the potentials of MSCs for tissue engineering and a number of clinical trials are now underway. Most of the emphasis on minimally invasive therapeutic alternatives including intraarticular injections of MSCs, aim to cut out cost and risks of major surgeries.

Eye Conditions

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This section is strictly to provide information.

A Promising Tool in Retina Regeneration: Current Perspectives and Challenges When Using Mesenchymal Progenitor Stem Cells in Veterinary and Human Ophthalmological Applications

Stem cells have been investigated in opthalmological research as a forthcoming tool for retinal degeneration. Mesenchymal stem cells (MSCs) have exhibited many advantages because of their multilineage differentiation potential, the ease in their culturing and their immunomodulatory properties which are crucial in retinal regeneration research. Current exploration has determined new mechanisms of regeneration and MSC protective capabilities, on degeneration of different types of retinal cell ad retinal vessels. Mesenchymal stem cell-derived microvesicles (MVs) allow for developments in future research and clinical applications as a result of their availability as well as the growth factors, miRNA and mRNA they possess. Studies have shown that the application of MVs in regenerative medicine proves to be very dynamic, which is directing clinical research in opthamology towards this domain of study. In the grand scheme of scientific interest, it is expected that MVs may have higher output and potential in retinal regeneration than stem cell therapies have so far, therefore it is anticipated that this research field will be moving further into this direction.

Therapeutic Potential of Mesenchymal Stem Cell-Derived Exosomes in the Treatment of Eye Diseases

Mesenchymal stem cells (MSCs) were, due to their immunomodulatory and pro-angiogenic characteristics, extensively explored as new therapeutic agents in cell-based therapy of uveitis, glaucoma, retinal and ocular surface diseases.Since it was recently revealed that exosomes play an important role in biological functions of MSCs, herewith we summarized current knowledge about the morphology, structure, phenotype and functional characteristics of MSC-derived exosomes emphasizing their therapeutic potential in the treatment of eye diseases. .In conclusion, MSC-derived exosomes represent potentially new therapeutic agents in the therapy of degenerative and inflammatory ocular diseases.

In the past decades, great interest has been shown in the development of new therapies for erectile dysfunction. Stem cell therapy has generated promising results in numerous preclinical trials in animal models, which is why it has led to the development of the first clinical trials in humans.

The main cause involved in the pathophysiology of erectile dysfunction is vascular damage related to endothelial and neuronal injury. The interest in stem cell therapy is justified by their capability to differentiate into specific damaged tissues, including endothelium and nervous tissue, and induction of the host own cell proliferation.

Stem-cell therapy for erectile dysfunction

Erectile dysfunction (ED) is the most common sexual disorder that men report to healthcare providers, and is the male sexual dysfunction that has been most investigated. Current treatments for ED focus on relieving the symptoms of ED and therefore tend to provide a temporary solution rather than a cure or reversing the cause.

The rapidly expanding and highly promising body of preclinical work on SC-based medicine providing a potential cure for ED, rather than merely symptom relief, is indicative of the increasing interest in regenerative options for sexual medicine over the past decade. Clinical trials are currently recruiting patients to test the preclinical results in men with ED.

Currently, the treatment of ED focuses on symptomatic relief of ED and therefore tends to provide temporary relief rather than providing a cure or reversing the underlying cause. Recently, stem cell-based therapies have received increasing attention regarding their potential for the recovery of erectile function. Preclinical studies have shown that these cells may reverse pathophysiological changes leading to ED rather than treating the symptom ED.

The development of methods to deliver stem cells to the penis has kindled a keen interest in understanding stem cell biology as it related to restoration of normal penile vascular and neuronal homeostasis. The use of stem cells for the treatment of ED represents an exciting new field.

Erectile dysfunction (ED) following radical prostatectomy (RP) is a result of inadvertent damage to the cavernous nerves that run close to the prostate capsula. Multipotent stromal cells (MSCs) are an attractive cell source for this application based on their regenerative potential and their clinical applicability. MSCs from both bone marrow and adipose tissue have shown beneficial effects in a variety of animal models for ED. While the type of model may influence the mechanisms of action of this MSC-based therapy, MSCs generally display efficacy in various animal models for ED.

Erectile dysfunction (ED) is still a common complication of radical prostatectomy. Current treatments of ED are mainly symptomatic. Mesenchymal stem cells (MSCs) have been widely investigated as a potential curative treatment. MSC therapy consistently improved erectile functions after cavernous nerve injury (CNI). There seems to be a consensus on the disease model used and outcome evaluation however further studies should be done.

Advances in stem cell research for the treatment of male sexual dysfunctions

This review summarizes recent literature on basic stem cell research in erectile dysfunction in cavernous nerve injury, aging, diabetes, and Peyronie’s disease and to provide a perspective on clinical translation of these cellular therapies. In summary, evidence from preclinical studies has established stem cells as a potential curative treatment for erectile dysfunction and early phase clinical trials are currently performed.

Stem Cells in Male Sexual Dysfunction: Are We Getting Somewhere?

Stem cells for sexual disorders are steadily being introduced into clinical trials. Two conditions of importance are the main target for this line of treatment, especially when regarding the wide array of translational and basic science highlighting the potential advantages of regenerative therapy: erectile dysfunction (ED) and more recently Peyronie disease (PD). Cellular therapy offers a treatment modality that might reverse disease progression. It would be used in a curative setting, in contrast to other pharmaceutical agents that are currently available.

This study concludes that stem cells have an established efficacy in preclinical studies and early clinical trials. Studies are currently being published demonstrating the safety of intrapenile injection of autologous bone marrow- and adipose tissue-derived stem cells.

Additional Research

Treatment of Psoriasis with Mesenchymal Stem Cells

Psoriasis is an incurable immune-mediated disease, which affects approximately 2% of the world’s population. Current treatments, including newly emerged biologic agents, have some limitations. In this study, they report two cases of psoriasis vulgaris treated by umbilical cord-derived mesenchymal stem cells (UC-MSCs). In these two cases, both of the patients remained relapse free over periods of several years.

Mesenchymal stem cells (MSCs) are multipotent cells that have the capability of differentiating into adipogenic, osteogenic, chondrogenic, and neural cells. With these multiple capabilities, MSCs have been highly regarded as effective transplantable cell source for regenerative medicine. Recent evidence demonstrates that Wharton’s jelly mesenchymal stem cells (WJ-MSCs) are potential transplantable cells for treatment of devastating diseases, such as cancer and diabetes. Their use in cell therapy will be an integral addition to the field of regeneration. WJ-MSCs have a multitude of benefits such as their high proliferation rate, lower doubling time, and ability to function with non-immune-suppressed animals.

Apart from cancer treatment WJ-MCSs also can facilitate cell-based therapies for liver diseases and diabetes mellitus due to their high proliferation and differentiation ability. For example, WJ-MSCs can express hepatoblastic phenotypes and can become liver cells or pancreatic cells.

Umbilical cord matrix or Wharton’s jelly-derived stromal cells (WJ-MSCs) are an easily accessible source of mesenchymal-like stem cells. This study shows that WJ-MSCs have trophic support properties and effectively modulate immune cell functioning both in vitro and in the EAE model, suggesting WJ-MSC may hold promise for MS therapy.

Role of Nonmuscle Myosin II in Migration of Wharton’s Jelly-Derived Mesenchymal Stem Cells

It is the promise of regeneration and therapeutic applications that has sparked an interest in mesenchymal stem cells (MSCs). Following infusion, MSCs migrate to sites of injury or inflammation by virtue of their homing property. To exert optimal clinical benefits, systemically delivered MSCs need to migrate efficiently and in adequate numbers to pathological areas in vivo. However, underlying molecular mechanisms responsible for MSC migration are still not well understood. The data in this study suggests that nonmuscle myosin II (NMII) acts as a regulator of cell migration and adhesion in Wharton’s jelly mesenchymal stem cells (WJ-MSCs).

Mesenchymal stromal/stem cells (MSCs) are multi-potent non-hematopoietic stem cells, residing in most tissues including the lung. MSCs have been used in therapy of chronic inflammatory lung diseases such as Cystic Fibrosis (CF), asthma, and chronic obstructive pulmonary disease (COPD) but the main beneficial effects reside in the anti-inflammatory potential of the released extracellular vesicles (EVs). Recent reports demonstrate that EVs are effective in animal model of asthma, E.coli pneumonia, lung ischemia-reperfusion, and virus airway infection among others. The general significance of this study suggests EVs could be a novel strategy to control the hyper-inflamed condition in Cystic Fibrosis.

Wharton’s jelly (umbilical cord matrix) was proved to be a rich source of MSCs and they can be isolated by non-invasive methods such as Ficoll density gradient and antibodies coupled magnetic beads without any ethical issues. This review summarizes the potential interaction of fetal mesenchymal stem cells with tumor cells and their use in clinical protocols.

Autologous Cellular Therapy and its Effects on COPD: A Pilot Study

Chronic Obstructive Pulmonary Disease (COPD) is a progressive lung disorder that often occurs as a result of prolonged cigarette smoking, second-hand smoke, and polluted air or working conditions. COPD is the most prevalent form of chronic lung disease. The physiological symptoms of COPD include shortness of breath (dyspnea), cough, and sputum production, exercise intolerance and reduced Quality of Life (QOL). These signs and symptoms are brought about by chronic inflammation of the airways, which restricts breathing. When fibrotic tissues contract, the lumen is narrowed, compromising lung function.

Initial studies of cells treatments show efficacy, lack of adverse side effects and may be used safely in conjunction with other treatments. This method of treatment serves as an alternative to expensive lung transplants that have a high probability of rejection by the body, which can create a new set of problems for patients. In a recent study of regenerative cellular therapy done by the University of Utah, patients exhibited improvement in PFTs and oxygen requirement compared to the control group with no acute adverse events.

COPD Improves with Stem Cell Therapy

Chronic obstructive pulmonary disease (COPD) is a progressive form of lung disease ranging from mild to severe and characterized by a restriction of airflow into and out of the lungs that makes breathing difficult. Two main forms of COPD are chronic bronchitis and emphysema. There is currently no cure for COPD, but treatment options such as stem cell therapy can prevent more damage and improve the patient’s quality of life.

Stem cell therapy is a strategy that introduces new adult stem cells into damaged tissue in order to treat disease or injury. The treatments have the potential to change the face of human disease and alleviate suffering. While stem cell therapy can help with COPD symptoms, it is not a definite cure for chronic lung disease. Still, for many patients, stem cell therapy is the best currently available treatment option.

In summary, the approaches discussed for regenerative therapies have demonstrated positive effects in chronic obstructive pulmonary disease (COPD) animal models and have been safe in clinical trials. However, greater effort must be taken to develop approaches that will lead towards a curing solution to COPD patients.

Stem cell therapy in chronic obstructive pulmonary disease. How far is it to the clinic?

Chronic obstructive pulmonary disease (COPD) is a respiratory disease that has a major impact worldwide. The currently-available drugs mainly focus on relieving the symptoms of COPD patients. However, in the latter stages of the disease, the airways become largely obstructed and lung parenchyma becomes destructed due to underlying inflammation. The inappropriate repair of lung tissue after injury may contribute to the development of disease. Studies suggest that cell-based therapies and novel bioengineering approaches may be potential therapeutic strategies for lung repair and remodeling. In this paper, they review the current evidence of stem cell therapy in COPD.

The clinical use of regenerative therapy in COPD

Regenerative or stem cell therapy is an emerging field of treatment based on stimulation of endogenous resident stem cells or administration of exogenous stem cells to treat diseases or injury and to replace malfunctioning or damaged tissues. Current evidence suggests that in the lung, these cells may participate in tissue homeostasis and regeneration after injury. The use of bone marrow-derived stem cells could allow repairing and regenerate the damaged tissue present in chronic obstructive pulmonary disease by means of their engraftment into the lung.

Cell therapies using various stem cells have been extensively evaluated. The lung is one of the easiest organs in which to instill exogenous cells because cells can be applied through both the airway and circulation. In addition, most of the intravenously instilled cells are trapped within the pulmonary circulation; therefore, the efficacy of cell delivery is naturally high.

Mesenchymal stem cells (MSCs) are the most extensively evaluated candidates for clinical cell-based therapy. Many clinical trials using MSCs have been registered and are ongoing. Autologous MSCs are easily isolated from the bone marrow and other tissues. MSCs are expected to reduce inflammation and promote the repair process. These beneficial effects are thought to be based on the ability of MSCs to modulate the immune system and their capacity to produce growth factors and cytokines, such as keratinocyte growth factor, HGF, and prostaglandin E2.

Because of these anti-inflammatory effects, a phase II clinical trial using MSCs has been performed in moderate and severe COPD patients. The trial successfully demonstrated the safety of cell therapies using MSCs and some reduction in the inflammatory response in COPD patients but did not show any beneficial effects on lung function. Additional studies, especially in early-stage COPD patients, are needed.

Stem cell therapy: the great promise in lung disease

Lung injuries are leading causes of morbidity and mortality worldwide. Pulmonary diseases such as asthma or chronic obstructive pulmonary disease characterized by loss of lung elasticity, small airway tethers, and luminal obstruction with inflammatory mucoid secretions. The use of adult stem cells to help with lung regeneration and repair could be a newer technology in clinical and regenerative medicine. In fact, different studies have shown that bone marrow progenitor cells contribute to repair and remodeling of lung in animal models of progressive pulmonary hypertension.

Current Status of Stem Cells and Regenerative Medicine in Lung Biology and Diseases

Lung diseases remain a significant and devastating cause of morbidity and mortality worldwide. In contrast to many other major diseases, lung diseases notably chronic obstructive pulmonary diseases (COPD), including both asthma and emphysema, are increasing in prevalence and COPD is expected to become the 3rd leading cause of disease mortality worldwide by 2020. New therapeutic options are desperately needed.

A rapidly growing number of investigations of stem cells and cell therapies in lung biology and diseases as well as in ex vivo lung bioengineering have offered exciting new avenues for advancing knowledge of lung biology as well as providing novel potential therapeutic approaches for lung diseases. These initial observations have led to a growing exploration of endothelial progenitor cells and mesenchymal stem (stromal) cells in clinical trials of pulmonary hypertension and chronic obstructive pulmonary disease (COPD) with other clinical investigations planned.

The tissue turnover of unperturbed adult lung is remarkably slow. However, after injury or insult, a specialized group of facultative lung progenitors become activated to replenish damaged tissue through a reparative process called regeneration. Disruption in this process results in healing by fibrosis causing aberrant lung remodeling and organ dysfunction. Post-insult failure of regeneration leads to various incurable lung diseases including chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis.

Endogenous and exogenous stem cells: a role in lung repair and use in airway tissue engineering and transplantation

Rapid repair of the denuded alveolar surface after injury is a key to survival. The respiratory tract contains several sources of endogenous adult stem cells residing within the basal layer of the upper airways, within or near pulmonary neuroendocrine cell rests, at the bronchoalveolar junction, and within the alveolar epithelial surface, which contribute to the repair of the airway wall. Bone marrow-derived adult mesenchymal stem cells circulating in blood are also involved in tracheal regeneration. However, an organism is frequently incapable of repairing serious damage and defects of the respiratory tract resulting from acute trauma, lung cancers, and chronic pulmonary and airway diseases. Therefore, replacement of the tracheal tissue should be urgently considered. The shortage of donor trachea remains a major obstacle in tracheal transplantation. However, implementation of tissue engineering and stem cell therapy-based approaches helps to successfully solve this problem.

Adult stem cells for chronic lung diseases

As a self‐repair mechanism, living organisms have stem cells that are attracted to sites of injury. Chronic injury as well as aging could exhaust and impair stem cell reparative capacity as well as diminish number of available stem cells. The mechanism(s) by which alterations in the homeostasis of stem cells pools are involved in the pathogenesis of chronic lung diseases is unknown. If stem cell exhaustion and aging is the cause of morbid states, stem cell‐based therapies will be able to prevent and treat them. Restoration of stem cells has shown promising therapeutic benefits for certain lung pathologies. Particularly, the immunomodulatory capacity of bone marrow‐derived mesenchymal stem cell (B‐MSC) has been shown to be beneficial for lung diseases with exacerbated inflammatory responses. However, a generalized use of B‐MSC in chronic lung diseases must be considered with caution, and careful studies are still required to establish safety and efficacy of such use.

Lung regeneration using amniotic fluid mesenchymal stem cells

Respiratory diseases, such as chronic obstructive pulmonary disease (COPD), pulmonary hypertension and lung fibrosis, are yet a major challenge in the world and they result in irreversible structural lung damage. Lung transplantation as the only therapeutic option face some major challenges like graft rejection and cancer, arising as a result of immunosuppression. A low survival rate faced by lung transplantation patients is presently limited to approximately 5 years. Lungs shortage therefore calls for a mechanism that would increase the availability of suitable organs for transplantation. In this review, we give an update on the use of amniotic fluid mesenchymal stem cells (AFMSCs) as an optimal source for lungs scaffold re-cellularization, due to their limitless accessibility and possibility for proliferation and differentiation. Further studies will be required in tissue engineering (TE) and regenerative medicine (RM), especially shifting our focus towards AFMSCs as a cell source for this regeneration.

This review summarizes the recent advances in stem cell treatments and the research efforts conducted through the application of stem cell therapy for respiratory system diseases. In particular, researchers have used animal models to gather data about treating lung injury by stem cell transplantation. This review concentrated on the findings about route, timing and adjustment of cell transplantation dose, optimum stem cell type selection and potency marker of cells as therapeutic agents.

Adult stem cells in the treatment of autoimmune diseases

The past decade has seen the introduction of many agents, especially biologics, which have allowed a more successful control of AD manifestations. However, the elusive aim of tolerance induction has not yet been achieved. It could be that through harnessing the complex and multifaceted potential of cellular-based therapies, especially HSCT, a ‘resetting‘ of auto-aggressive immune reactions while maintaining protective immunity will be possible. In addition, the anti-proliferative and immunomodulatory properties of MSCs combined with their immunological privilege and seemingly low toxicity may offer a new strategy for controlling and protecting vital organs from inflammatory, destructive autoimmune reactions.

Treatment of severe autoimmune disease by stem-cell transplantation

Transplantation of haematopoietic stem cells — cells capable of self renewing and reconstituting all types of blood cell — can treat numerous lethal diseases, including leukaemias and lymphomas. It may now be applicable for the treatment of severe autoimmune diseases, such as therapy-resistant rheumatoid arthritis and multiple sclerosis. Studies in animal models show that the transfer of haematopoietic stem cells can reverse autoimmunity, and several mechanistic pathways may explain this phenomenon.

A lethal autoimmune disease succumbs to stem cells

In this study, they review how stem cell transplants can help people to survive a rare and deadly form of the autoimmune disease scleroderma.

Scleroderma causes the skin to harden and become immobile. In its most severe form, it affects the internal organs, and is usually fatal. Individuals who receive conventional drug therapy today are no more likely to survive the disease than patients 40 years ago.

The results of this study are consistent with two previous stem-cell trials, and should help to establish stem-cell transplants as a standard treatment for individuals with severe scleroderma, according to the researchers.

Open-field test scores of spinal cord injured rats treated with human cord blood at 5 days were significantly improved as compared to scores of rats similarly injured but treated at day 1 as well as the otherwise untreated injured group. The results suggest that cord blood stem cells are beneficial in reversing the behavioral effects of spinal cord injury, even when infused 5 days after injury. Human cord blood-derived cells were observed in injured areas, but not in non-injured areas, of rat spinal cords, and were never seen in corresponding areas of spinal cord of non-injured animals. The results are consistent with the hypothesis that cord blood-derived stem cells migrate to and participate in the healing of neurological defects caused by traumatic assault.

In this study, they show that the transplantation of bone marrow mononuclear cells (BMNCs) restored the vascularity and function of diabetic nerves, supporting the hypothesis that neural vascularity is pathophysiologically associated with the development and reversal of diabetic neuropathy (DN).

The identification of mesenchymal stem cell (MSC) sources that are easily obtainable is of utmost importance. Several studies have shown that MSCs could be isolated from umbilical cord (UC) units. However, the presence of MSCs in umbilical cord blood (UCB) is controversial. A possible explanation for the low efficiency of MSCs from UCB is the use of different culture conditions by independent studies. In this study, they compared the efficiency in obtaining MSCs from unrelated paired UCB and UC samples harvested from the same donors.

This study concluded that in a murine model of acute kidney injury (AKI), human cord blood mesenchymal stem cell (hCB‐MSC) treatment promotes kidney regeneration and prolongs survival better than any other cellular approach attempted so far. These effects appear to be mediated by a paracrine action of hCB‐MSCs on tubular cells involving lowering oxidative stress, apoptosis, and inflammation. These data indicate that hCB‐MSCs have to be considered as one possible future option for cellular therapy of AKI in humans.

This is the first study to provide evidence that intracoronary delivery combined with multiple intravenous infusions of umbilical cord‐derived mesenchymal stromal cells (UC‐MSCs) improves left ventricular (LV) function, perfusion, and remodeling in a large animal model of chronic myocardial ischemia. In the present study, we observed neither tumor nor teratoma formation in human UC‐MSC‐transplanted animals, and no sustained ventricular arrhythmia or anaphylaxis was observed. Because these cells can be isolated from medical waste, expanded, banked, and administered to patients at any time without immunological rejection, human UC‐MSCs might be an ideal cell source for cardiac cell therapy and hold promise as an off‐the‐shelf product.

This is the first phase in a study of rheumatoid arthritis (RA) patients that evaluated the safety and tolerability of a single intravenous infusion with human umbilical cord blood‐derived mesenchymal stem cells (hUCB‐MSCs) and with cell numbers of up to 1 × 108, revealing an acceptable safety profile. Conclusions regarding efficacy in phase I trials are limited, and although evaluation of disease activity was not the primary objective of this study, a single infusion of hUCB‐MSCs effectively reduced the mean DAS28 at week 4. Considering favorable safety profiles, intravenous infusion of hUCB‐MSCs may constitute a therapeutic option for patients with RA, who are refractory to or intolerant of methotrexate (MTX). There is a wide array of opportunities for future clinical studies with different hUCB‐MSC infusion strategies in which safety profiles should be carefully monitored and outcome measures further refined for optimized effectiveness evaluations.

Animal and human studies have suggested the potential of mesenchymal stromal cells (MSCs) to treat systemic lupus erythematosus (SLE). In this study, they present the results of compassionate MSC treatments for three SLE patients to provide the proof of concept for a randomized and controlled clinical trial.

The ability of mesenchymal stem cells (MSCs) to positively influence processes such as immunosuppression, angiogenesis and inflammation generated a lot of interest and enthusiasm from clinicians and researchers alike. It is apparent that many questions remain unanswered, however what is becoming clear is that MSCs-based therapy should considered as a safe and potentially efficient therapeutic option in the management of advanced stage of systemic sclerosis (SSc).

The Use of Human Mesenchymal Stem Cells as Therapeutic Agents for the in vivo Treatment of Immune-Related Diseases: A Systematic Review

In this systematic review, the treatment of many types of immune-related diseases was conducted through the administration of human mesenchymal stem cells (hMSCs). Positive results were usually reported and attributed to the paracrine effects of molecules secreted by hMSCs on immune cells. In conclusion, despite the need for further studies, the treatment of immune-related diseases through the administration of hMSCs is progressively ceasing being only a promising possibility and becoming a reality.

The Beneficial Effect of Human Amnion Mesenchymal Cells in Inhibition of Inflammation and Induction of Neuronal Repair in EAE Mice

Accumulating evidence showed that mesenchymal stem cells (MSCs) from different origins, including adipose-derived, bone marrow-derived, and umbilical cord-derived, could attenuate the disease progression in EAE animal models. Furthermore, autologous bone marrow-derived MSCs transplantation and allogeneic umbilical cord-derived MSCs transplantation for the treatment of MS have been proved safe and effective in clinical trials, which showed that treatment improved the course of the disease, reduced the inflammatory response, and promoted neuroprotection.

Multipotent mesenchymal stromal cells (MSCs) represent a promising cell-based therapy in regenerative medicine and for the treatment of inflammatory/autoimmune diseases. Importantly, MSCs have emerged as an important contributor to the tumor stroma with both pro- and anti-tumorigenic effects.

Modulation of autophagy as new approach in mesenchymal stem cell-based therapy

In this study, they review the current literature describing mechanisms by which modulation of autophagy strengthens pro-angiogenic and immunosuppressive characteristics of mesenchymal stem cells (MSCs) in animal models of multiple sclerosis, osteoporosis, diabetic limb ischemia, myocardial infarction, acute graft-versus-host disease, kidney and liver diseases. Obtained results suggest that modulation of autophagy in MSCs may represent a new therapeutic approach that could enhance efficacy of MSCs in the treatment of ischemic and autoimmune diseases.

Mesenchymal stem cells (MSCs) have been intensively studied and applied in regenerative medicine and tissue engineering. Recently, their immune modulation functions make them as attractive potential approaches for autoimmune disease treatment. Systemic lupus erythematosus (SLE) is one type of chronic autoimmune diseases with multi-organ damaged by the immune system. Although current available treatments are effective for some patients, others are refractory for these therapies. The immuno-modulatory and regenerative characteristics of MSCs make them as one promising candidate for treating SLE.

Cell therapies for refractory rheumatoid arthritis

Cell-based therapies have become the focus, attracting more attention due to their potential for remission induction. Several immune-regulatory cell types, such as haematopoietic stem cells, mesenchymal stem cells and regulatory T cells have been defined as novel targets.

Mesenchymal stem cells (MSCs) from systemic lupus erythematosus (SLE) patients have demonstrated defects such as aberrant cytokine production. Moreover, impaired phenotype, growth and immunomodulatory functions of MSCs from patients with SLE in comparison to healthy controls have been reported. Therefore, it is hypothesized that SLE is potentially an MSC-mediated disease and, as a result, allogeneic rather than autologous MSC transplantation can be argued to be a potentially advantageous therapy for patients with SLE.

Recently, growing evidence suggests that the functions of hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) are disrupted in SLE pathology. And HSC or MSC transplantation (HSCT/MSCT) can offer an effective and safe therapy for the severe SLE patients, resulting in disease clinical remission and improvement of organ dysfunction.

A higher level of expression of anti-apoptotic and antioxidant enzymes was noted in the ovaries of groups treated with human umbilical cord mesenchymal stem cell (hUCMSCs). These parameters were enhanced more when mice were treated with hUCMSCs for 1 month than when they treated with hUCMSCs for 2 weeks. IV was better able to restore ovarian function than MI. These results suggest that both methods of transplantation may improve ovarian function and that IV transplantation of hUCMSCs can significantly improve ovarian function and structural parameters more than MI transplantation of hUCMSCs can.

Human umbilical cord mesenchymal stem cells (hUCMSCs) are a type of pluripotent stem cell which are isolated from the umbilical cord of newborns. hUCMSCs have great therapeutic potential. This experimental study was designed in order to investigate whether the transplantation of hUCMSCs can improve the ovarian reserve function of perimenopausal rats and delay ovarian senescence.

Stem cells provide a promising candidate for the treatment of the fatal pediatric dilated cardiomyopathy (DCM). This study aimed to investigate the effects of intramuscular injection of human umbilical cord-derived mesenchymal stem cells (hUCMSCs) on the cardiac function of a DCM rat model.

This study has provided evidence that intramuscular injection of hUCMSCs in DCM rats can improve cardiac function and attenuate cardiomyocyte damage by regulating the expression and secretion of multiple tissue repair-related cytokines via paracrine mechanisms. Therefore, intramuscular injection of MSCs may be a promising candidate treatment for pediatric DCM as a minimally invasive approach.

Long term effect and safety of Wharton’s jelly-derived mesenchymal stem cells on type 2 diabetes

The findings of the present study suggested thatWharton’s jelly-derived mesenchymal stem cells (WJ-MSC) infusion may effectively ameliorate hyperglycemia, improve islet β-cell function and reduce the incidence of diabetic complications over a sustained period of time. Despite the fact that WJ-MSC infusion does not appear to attenuate insulin resistance, WJ-MSC infusion may have therapeutic potential as a novel agent for the treatment of type 2 diabetes mellitus (T2DM).

A total of 61 patients with T2DM were randomly divided into two groups on the basis of basal therapy; patients in group I were administered WJ-MSC intravenous infusion twice, with a four-week interval, and patients in group II were treated with normal saline as control. During the 36-month follow-up period, the occurrence of any adverse effects and the results of clinical and laboratory examinations were recorded and evaluated. The lack of acute or chronic adverse effects in group I was consistent with group II. Blood glucose, glycosylated hemoglobin, C-peptide, homeostasis model assessment of pancreatic islet β-cell function and incidence of diabetic complications in group I were significantly improved, as compared with group II during the 36-month follow-up.

The results of the present study demonstrated that infusion of WJ-MSC improved the function of islet β-cells and reduced the incidence of diabetic complications, although the precise mechanisms are yet to be elucidated. The infusion of WJ-MSC may be an effective option for the treatment of patients with type 2 diabetes.

Mesenchymal stem cells in tissue repair

The advent of mesenchymal stem cell (MSC)-based therapies for clinical therapeutics has been an exciting and new innovation for the treatment of a variety of diseases associated with inflammation, tissue damage, and subsequent regeneration and repair. Application-based ability to measure MSC potency and fate of the cells post-MSC therapy are the variables that confound the use of MSCs therapeutics in human diseases. An evaluation of MSC function and applications with attention to detail in the preparation as well as quality control and quality assurance are only as good as the assays that are developed. This study reviews some of the in vitro and in vivo assays for MSC function and activity and their application to the clinical arena.

Mesenchymal stem cells (MSCs) are promising tools for the treatment of diseases such as infarcted myocardia and strokes because of their ability to promote endogenous angiogenesis and neurogenesis via a variety of secreted factors. MSCs found in the Wharton’s jelly of the human umbilical cord are easily obtained and are capable of transplantation without rejection. In this study, they isolated MSCs from Wharton’s jelly and bone marrow (WJ-MSCs and BM-MSCs, respectively) and compared their secretomes.

This results of this study suggest that WJ-MSC, because of a unique secretome, is a better MSC source to promote in vivo neurorestoration and endothelium repair.

Rheumatoid arthritis (RA) is a T-cell-mediated systemic autoimmune disease, characterized by synovium inflammation and articular destruction. Bone marrow mesenchymal stem cells (MSCs) could be effective in the treatment of several autoimmune diseases. However, there has been thus far no report on umbilical cord (UC)-MSCs in the treatment of RA. This study evaluates the potential immunosuppressive effects of human UC-MSCs in RA.

The study concluded that human UC-MSCs suppressed the various inflammatory effects of fibroblast-like synoviocytes (FLSs) and T cells of RA in vitro.

Stem cell delivery of therapies for brain disorders

The blood brain barrier (BBB) poses a problem to deliver drugs for brain malignancies and neurodegenerative disorders. Stem cells such as neural stem cells (NSCs) and mesenchymal stem cells (MSCs) can be used to delivery drugs or RNA to the brain. This use of methods to bypass the hurdles of delivering drugs across the BBB is particularly important for diseases with poor prognosis such as glioblastoma multiforme (GBM).

In conclusion, MSCs have the potential as cellular vehicles for drugs and other molecules to treat patients with neural diseases such as GBM, and other neuropathologies for which limited treatment options exist. When considering the limitations of current methods of drug delivery to the brain, MSCs have the potential to become a safe cellular delivery vehicle containing a prodrug as well as ectopically expressed genes for targeted delivery. The affinity for MSCs to migrate to the brain combined with the relative ease for expanded MSCs make them attractive for gene and drug delivery.